大鼠脊髓内EGFR表达与PI3K/AKt/mTOR活性的发育相关变化

Development-related changes of EGFR expression and PI3K/AKT/mTOR pathway activities in the rat spinal cords

目的研究脊髓组织神经元的内在生长活性发育依赖性丢失的可能机制。方法利用免疫荧光染色、Western blot和PCR等方法检测神经系统不同发育时期(胚胎期、新生期和成熟期)脊髓组织中EGFR的表达以及PI3K/Akt/mTOR活化状态,并分析相互之间的关系。结果在神经系统发育成熟过程中,EGFR的表达水平在出生前达到高峰,出生后逐渐降低,成熟期后始终维持在一个较低的水平;PI3K/AKt信号通路活性增强的同时EGFR表达的上调及mTOR表达增加。出生后随着EGFR表达的下调,PI3K/AKt通路活性以及mTOR的表达也随之减弱。结论脊髓组织中PI3K/AKt信号通路的活性与中枢神经系统的发育成熟有关,EGFR下调导致PI3K/AKt/mTOR的活性降低可能是中枢神经系统内在生长活性发育依赖性丢失的原因之一。

Objective To explore the correlation between EGFR expression and PI3K/Akt/mTOR pathway activities in rat spinal cords of different developmental stages. Methods Evaluated EGFR expression and PI3K/Akt/mTOR activities by immunofluorescence, western blot and PCR in embryo, newborn, and adult rat spinal cord tissues. Results During the development of nervous system, the EGFR expression level reached its peak before birth, declined gradually afterwards and maintained at a low level upon maturation. Both PI3K/Akt activities and mTOR expression increased prior to birth. The pathway activities reduced in parallel to EGFR changes after birth. Conclusion The activities of PI3K/AKT signaling pathway in spinal cord tissues likely correlated with the maturity of central nervous system. Decreased PI3K/AKT/mTOR pathway activities, which possibly resulted from the downregulation of EGFR, may be one of reasons for the loss of intrinsic growth-dependent development in central neurons system.